Methyl Tetra Hydro Folate Reductase Enzyme Polymorphism in the Mothers with Previous Autosomal Aneuploidy Birth in the Indigenous African Population of Northern Region of South Africa

Abstract

IntroductionAneuploidy is a genetic disorder where the total number of chromosomes is either less or more than the normal diploid number of 46, XX or 46, XY [1]. The most common aneuploidies in South Africa caused by autosomal chromosomal abnormalities include Down syndrome (Trisomy 21), Edward syndrome (Trisomy 18) and Patau syndrome (Trisomy 13). Globally the incidence for Down syndrome is about 1 in 650 to 1000 live births [2], Edward syndrome is 1 in 6000 live birth [3], and Patau is between 1 in 5000 to 29000 live birth [4]. Currently the prevalence rate is 1 out of 500 live birth for Down syndrome in South Africa with 1886 new cases diagnosed every year [5] and for Edward syndrome the prevalence is 1 in 4000 live birth and Patau is 1 in 8889 live birth [6,7]. The aetiology of these autosomal aneuploidies are believed to be due to non-disjunction of chromosome in maternal ovum during meiosis which is thought to be a sporadic, incidental event usually associated with older age group mothers. Notably, there is an increased incidence of aneuploidy babies has been observed in younger age group mothers with less than 35 years of age in South African black population [8].There were studies done in the Middle East families with recurrence aneuploidy births to determine if there is a genetic link. Krishna Murthy and Farag reported two unrelated Kuwaiti families each having 3 siblings with trisomy 21 as a result the researchers suggested that some genetic predisposition and gonadal mosaicism could be the underlying cause of recurrent aneuploidy in the younger mothers, thus increasing the risk of recurrence of such pregnancies [9]. There were studies that found that a particular polymorphism of one of these genes Methylenetetrahydrofolate reductase (MTHFR) might be a maternal risk factor for having child with Aneuploidy or Down syndrome and that a significant increase in plasma homocysteine levels exists in mothers of the children with Aneuploidy or Down syndrome [10,11].Increased homocysteine may result from dietary deficiency of folate and or vitamin B12 or from genetic polymorphism of Methylenetetrahydrofolate reductase (MTHFR). These genes encode the enzymes involved in the transfer of methyl group from sulpha containing amino acids (homocysteine and cysteine). Decreased transfer results in decrease methylation of DNA around the centromere region of chromosome 21, 18 and 13 proposed to be leading to aneuploidy. This hypothesis has led many researchers to further explore the evidence between DNA methylation of chromosome 21, 18, 13 in the unfertilized ovum but due to invasive nature of method involved in acquiring the pre-implementation studies, it has not been proven [10,[12][13][14][15][16].Indirect evidence of younger mothers having high level of plasma homocysteine with or without genetic polymorphisms would be the closest link to identifying the risk of recurrence aneuploidy in the AbstractBackground and purpose of the study: Aneuploidy births are highly prevalent in our population and some families, recurre...